Background: Environment and lifestyle contribute to the development of asthma in children. Understanding the relevant factors in this relationship may provide methods of prevention. The role of diet ...in the development of asthma in pre-school children was investigated. Methods: Data from 2978 children participating in a prospective birth cohort study were used. Food frequency data were collected at the age of 2 years and related to asthma symptoms reported at the age of 3 years. Results: The prevalence of recent asthma at age 3 was lower in children who consumed (at age 2) full cream milk daily (3.4%) than in those who did not (5.6%) and in those who consumed butter daily (1.5%) than in those who did not (5.1%). The prevalence of recent wheeze was lower in children who consumed milk products daily (13.7%) than in those who did not (18.4%) and in children who consumed butter daily (7.7%) than in those who did not (15.4%). These effects remained in a logistic regression model including different foods and confounders (adjusted odds ratio (CI) for recent asthma: full cream milk daily v rarely 0.59 (0.40 to 0.88), butter daily v rarely 0.28 (0.09 to 0.88)). Daily consumption of brown bread was also associated with lower rates of asthma and wheeze, whereas no associations were observed with the consumption of fruits, vegetables, margarine, and fish. Conclusions: In pre-school children, frequent consumption of products containing milk fat is associated with a reduced risk of asthma symptoms.
Respiratory syncytial virus (RSV) infection has been shown to be a risk factor for the development of allergy in humans and mice. The allergy-enhancing properties of RSV may be dependent on atopic ...background and an individual's history of RSV infection. We examined the influence of the timing of infection and prior inoculation with RSV in a mouse model of allergic asthma. Mice were sensitized to and challenged with ovalbumin (OVA) and were inoculated with RSV either before or during the sensitization or challenge period. One group of mice was inoculated with RSV both before sensitization to OVA and during challenge with OVA. Increased pulmonary expression of interleukin (IL)-4, IL-5, and IL-13 mRNA and aggravated alveolitis and hypertrophy of mucus-producing cells were observed only when OVA-sensitized mice were inoculated with RSV shortly before or during challenge with OVA. Despite protection against viral replication, prior inoculation with RSV did not abrogate RSV-enhanced, OVA-induced expression of T helper 2 (Th2) cytokines in the lung. In conclusion, inoculation with RSV enhances allergic disease only when the immune system has already been Th2-primed by the allergen (i.e., OVA). This RSV-enhanced allergy is not completely abrogated by prior inoculation with RSV.
Context: The prevalence of allergic diseases has increased considerably over the last decades. The hygiene hypothesis has emerged, linking reduced microbial exposure and infections early in life with ...the development of allergic diseases. Especially some of currently available non-replicating infant vaccines are unlikely to mimic a natural infection-mediated immune response that protects against the development of allergic diseases. Moreover, several studies suggested infant vaccinations to increase the risk of allergic diseases.
Objective: To determine whether infant vaccinations increase the risk of developing allergic disease.
Data Sources: We searched MEDLINE from 1966 to March 2003 and bibliography lists from retrieved articles, and consulted experts in the field to identify all articles relating vaccination to allergy.
Study Selection and Data Extraction: We selected epidemiological studies with original data on the correlation between vaccination with diphtheria, pertussis, tetanus (DPT), measles, mumps, rubella (MMR) and Bacillus Calmette-Guérin (BCG) vaccine in infancy and the development of allergic diseases, and assessed their quality and validity.
Data Synthesis: Methodological design and quality varied considerably between the studies we reviewed. Many studies did not address possible confounders, such as the presence of lifestyle factors, leaving them prone to bias. The studies that offer the stronger evidence, including the only randomized controlled trial at issue published to date, indicate that the infant vaccinations we investigated do not increase the risk of developing allergic disease. Furthermore, BCG does not seem to reduce the risk of allergies.
Conclusions: The reviewed epidemiological evidence indicates that, although possibly not contributing to optimal stimulation of the immune system in infancy, current infant vaccines do not cause allergic diseases.
Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the ...development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n approximately 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 micro m in aerodynamic diameter, and "soot") at the home of each subject of the cohort. Questionnaire-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before 1 year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed.
Immunophenotyping of blood lymphocytes is an important tool in the diagnosis of hematologic and immunologic disorders. Because of maturation and expansion of the immune system in the first years of ...life, the relative and the absolute size of lymphocyte subpopulations vary during childhood. Therefore we wished to obtain reference values for the relative and the absolute size of all relevant blood lymphocyte subpopulations in childhood.
We used the lysed whole blood method for analysis of lymphocyte subpopulations in 429 blood samples from neonates (n = 20), healthy children (n = 358), and adults (n = 51). The following age groups were used: 1 week to 2 months (n = 13), 2 to 5 months (n = 46), 5 to 9 months (n = 105), 9 to 15 months (n = 70), 15 to 24 months (n = 33), 2 to 5 years (n = 33), 5 to 10 years (n = 35), and 10 to 16 years (n = 23).
Our results show that the absolute number of CD19+ B lymphocytes increases twofold immediately after birth, remains stable until 2 years of age, and subsequently gradually decreases 6.5-fold from 2 years to adult age. The CD3+ T lymphocytes increase 1.5-fold immediately after birth and decrease threefold from 2 years to adult age. The absolute size of the CD3+/CD4+ T-lymphocyte subpopulation follows the same pattern as the total CD3+ population, but the CD3+/CD8+ T lymphocytes remain stable from birth up to 2 years of age, followed by a gradual threefold decrease toward adult levels. In contrast to B and T lymphocytes, the absolute number of natural killer cells decreases almost threefold in the first 2 months of life and remains stable thereafter. Our study also showed that changes in the absolute size of lymphocyte subpopulations are not always consistent with changes in their relative size. This demonstrates that the relative counts of lymphocyte subsets do not reflect their actual size and are therefore of limited value.
On the basis of this study we strongly recommend that immunophenotyping of blood lymphocytes for the diagnosis of hematologic and immunologic disorders be based on the absolute rather than on the relative size of lymphocyte subpopulations. Our data can be used as age-matched reference values for blood lymphocyte immunophenotyping.
Background The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood.
Objective To analyse the ...environmental and genetic risk factors and immunological responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high‐risk children.
Methods High‐risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were analysed for their proliferative and cytokine responses after polyclonal and allergen‐specific stimulation.
Results At 12 months of age 25% children had developed an atopic disease. Two atopic parents, parental smoking and atopic dermatitis of at least one of the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4+CD45RO+ cells and an increased polyclonal‐stimulated proliferation were observed. Furthermore, an impaired allergen‐induced, but not polyclonal‐stimulated IFN‐γ production was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL‐4, IL‐5, and IL‐13) after both polyclonal and, to a lesser extent, allergen‐specific stimulation was found in the children developing atopy. Allergen‐induced IL‐10 production at 12 months of age was only observed in the non‐atopic children.
Conclusion Our data indicate that the first 6 months of life represent a critical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine profile in high‐risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen‐induced IFN‐γ production in the neonatal period. Furthermore, the decreased allergen‐induced IL‐10 levels observed in the atopic children at 12 months of age may result in a lack of down‐regulation of the inflammatory process.
Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)–4 and IL-4 receptor α (IL-4Rα) genes, ...providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)–α, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 −592C or −592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio OR, 1.73 vs. 2.55; 95% confidence interval CI, 1.13–2.66 vs. 1.21–5.39). In children hospitalized at ⩽6 months of age, a significant association between RSV bronchiolitis and the IL-10 −592C allele was found (OR, 1.61; 95% CI, 1.10–2.35). No significant associations of TNF-α and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Rα Q551R and IL-10 C−592A polymorphisms
Summary
Background
It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease.
Objective
We investigated whether birth characteristics ...and environmental factors are associated with the development of atopic dermatitis in the first year of life.
Methods
Seventy‐six children with and 228 without atopic dermatitis, all children of mothers with respiratory allergy or asthma (PIAMA birth cohort study) were included in the study. Atopic dermatitis was defined as a positive history of an itchy skin condition with at least two of the following characteristics: visible dermatitis, history of outer arms/leg involvement, or general dry skin. Multiple logistic regression analysis was performed to study the independent effects of various risk factors.
Results
A birth weight 4000 g compared to 3000–4000 g was a significant risk factor for atopic dermatitis (odds ratio (OR)=2.4; 95% CI: 1.1–5.1) as was day care attendance (OR=2.9; 95% CI: 1.5–5.9). Exclusive breastfeeding in the first 3 months was negatively associated with atopic dermatitis (OR=0.6; 95% CI: 0.3–1.2), especially with visible dermatitis (OR=0.4; 95% CI: 0.2–1.0). Gender, gestational age, the presence of siblings or pets, and parental smoking were not significantly associated with atopic dermatitis.
Conclusion
This study shows that a high birth weight and day care attendance increase the risk of atopic dermatitis in the first year of life, while exclusive breastfeeding is a protective factor when dermatitis is found on inspection.
The association of variants of genes encoding interleukin (IL)–4 and the IL-4 receptor α chain (IL-4Rα) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. ...Polymorphisms in IL-4 (C−590T) and IL-4Rα (I50V and Q551R) were genotyped by restriction fragment–length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study). Results were also analyzed in a combination of these 2 tests, using Fisher’s method. The IL-4 590T allele was found more frequently among children hospitalized with RSV than expected in the case-control (odds ratio OR, 1.43; P=.04) and combination (OR, 1.41; P=.02) tests. Among children who were >6 months old when they were hospitalized, compared with the control group or with the <6 months old who were hospitalized for RSV infection, higher frequencies of both the IL-4 590T allele and the IL-4Rα R551 allele were found. These results indicate that gain-of-function variants of T helper type 2 cytokine genes may play a role in increasing the severity of RSV disease, which appears more pronounced after the first half-year of life
To investigate the association between contacts with other children and the development of respiratory infections in the first year of life in children with or without genetic predisposition for ...allergy.
Children (n = 4146) who participate in a prospective birth cohort study (Prevention and Incidence of Asthma and Mite Allergy study) were investigated. Questionnaires were used to obtain information on doctor-diagnosed upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI), child care attendance, having siblings, family history of allergic disease, and various potential confounders.
Child care attendance in the first year of life was associated with doctor-diagnosed URTI (adjusted odds ratio AOR: 2.7; 95% confidence interval CI: 2.1-3.4 for large child care facility vs no child care) and doctor-diagnosed LRTI (AOR: 5.6; 95% CI: 3.9-7.9). Having siblings was associated with doctor-diagnosed LRTI (AOR: 2.6; 95% CI: 2.0-3.4). In addition, children who have allergic parents and attend child care or have older siblings have a higher risk of developing doctor-diagnosed LRTI than do children who have nonallergic parents.
Child care attendance or having siblings increases the risk of developing doctor-diagnosed LRTI in the first year of life to a greater extent in allergy-prone children than in children who are not allergy prone.
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